tbuckley/cabot-search huggingface dataset:
Abstract 15765: Left Ventricular Strain on Echocardiogram is Associated With Abnormal Cardiac MRI Findings in Pediatric Patients With Covid-19
Authors: Summer Rye-Buckingham, Salima Bhimani, Terrie Vasilopoulos, Curt G Degroff, Jennifer G Co-Vu
Journal: Circulation (2022)

Introduction: Cardiac injury in COVID-19 may manifest as myocarditis, cardiomyopathy, ventricular arrhythmia, heart failure or cardiogenic shock. Although cardiac manifestations of COVID-19 is known, there is little literature regarding myocardial involvement in pediatric patients with COVID-19. Adult studies have suggested up to 80% of patients who have recovered from COVID-19 have abnormal cardiac MRI (CMR) findings. They have also suggested that up to 80% of adult patients hospitalized with COVID-19 have abnormal left ventricular global longitudinal strain (LV-GLS) and have used this to determine the extent of myocardial involvement. These findings can indicate potential long term cardiac sequalae. Our aim was to assess if abnormal LV-GLS from echocardiogram correlates with abnormal CMR findings in pediatric patients with history of COVID-19. Methods: This study is an IRB-approved retrospective chart review of pediatric patients less than 18 years old with a history of COVID-19 with evaluation of CMR and transthoracic echocardiograms (TTE) from 2020-2022. LV ejection fraction (LVEF) and LV-GLS were analyzed from TTE. CMR data includes LVEF, late gadolinium enhancement (LGE), parametric mapping (T1, T2 and extracellular volume). Comparisons between patient groups were made using Student's t-test, and p&lt;0.05 was considered statistically significant. Results: Of the 47 patients with history of COVID-19, 24 patients were analyzed (mean age 14 + 4 years). All patients had preserved LVEF by TTE and CMR. 13 patients had abnormal CMR findings including LGE, and/or abnormal parametric mapping. In these 13 patients, mean LV-GLS was -16.6 + 2.1 (95%CI: -17.6, -15.5). Of the 11 patients with normal CMR findings, the mean LV-GLS was -19.3 + 2.9 (95%CI: -20.9, -17.8). There was significant difference in LV-GLS when comparing patients with CMR abnormalities versus those with normal CMR (t=-3.2, df=32, p=0.003). Conclusions: Abnormal LV-GLS on TTE despite normal LVEF may be associated with abnormal CMR findings in patients with a history of COVID-19. These findings suggest that cardiac involvement may persist in pediatric patients who had recovered from COVID-19. This may have implications on which patients will need CMR imaging and long-term follow-up.
Abstract 15420: Cgas-Sting Pathway-Mediated Cholesterol Metabolism Promotes Atherosclerosis Formation
Authors: Yang Li, Chen Zhang, wei luo, Kimberly Rebello, Abhijit Chakraborty, Yanming Li, Lin Zhang, Hernan Vasquez, Joseph S Coselli, Alan Daugherty, Scott A LeMaire, Hong Lu, Ying H Shen
Journal: Circulation (2022)

Introduction: The mechanisms underlying macrophage lipid accumulation and foam cell formation, the critical step in atherosclerosis initiation, remain to be understood. The cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) signaling pathway triggers potent inflammation in response to cytosolic DNA accumulation. Hypothesis: In this study, we found that the cGAS-STING signaling pathway can promote macrophage lipid accumulation and atherosclerosis development. Methods: We developed an atherosclerosis mice model by a single intraperitoneal injection of an adeno-associated virus (AAV) containing a mouse PCSK9 gain-of-function mutation D377Y. Results: In the descending aorta of patients and aortic root of atherosclerotic mice, we detected profound cytosolic DNA accumulation that was associated with the activation of cGAS -STING in both human and mouse atherosclerotic plaques. In cultured macrophages, DNA uptake by macrophages activated the cGAS-STING pathway, which induced the biosynthesis of fatty acids and cholesterol. Interestingly, we found that STING can bind to SREBP2 (sterol regulatory element-binding protein 2) through SCAP (SREBP2 cleavage activating protein) and promote its cleavage and nuclear translocation, and subsequent induction of genes in fatty acid and cholesterol biosynthesis. Finally, in an AAV-PCSK9/high-fat diet-induced atherosclerosis model, cGas -/- and SMC- Sting -/- mice exhibited a reduction of SREBP2 activation and lipid content in macrophages and a reduction in atherosclerosis burden. Conclusions: Our findings indicated that DNA and cGAMP from damaged cells serve as a danger molecule that, by activating the cGAS-STING cytosolic DNA sensing signaling, promotes macrophage lipid biosynthesis and accumulation, contributing to atherosclerosis development.
Abstract 15278: Transcatheter Closure of Atrial Septal Defect Over the Age of 60
Authors: Olga Hajnalka H Balint, Dorottya Kecskemeti, Zsolt Nagy, Balazs Szabo, Andras Temesvari
Journal: Circulation (2022)

Introduction: The long-term benefits of transcatheter device closure of a secundum atrial septal defect (ASD) over 60 remain controversial. The aim of the study was to assess the predictors of death late after device closure in these elderly patients. Methods: This retrospective study enrolled 87 patients with successful ASD transcatheter closure over 60 and at least 1 year follow-up after closure. The mean age was 73.3±5 years, and 74 of them were female (85%). All patients had an isolated secundum ASD with a mean defect size of 18±4 (9-30) mm. At the time of closure 10 patients were known with pulmonary hypertension (11%), 52 with atrial arrhythmia (61%), 56 with heart failure (64%), and 15 with coronary artery disease (17%). Demographic, clinical and echo data were compared between values at the time of closure, and at the last follow-up. Predictors of death were analyzed with multivariate Cox regression. Results: After the mean follow-up of 5±4 years 11 patients developed high LV filling pressure, 15 patients had new atrial arrhythmia and 10 patients right heart failure. At the last FU a significant decrease in right ventricular (45±5 vs 38±8 mm, p=0.032) and right atrium dimension (62±10 vs. 59 ±10mm, p=0.045) were seen, together with right ventricular systolic pressure improvement (51±18 vs. 40±19 mmHg, p=0.038). The left atrium showed significant further dilatation after closure (60±9 vs. 62±9.5, p=0.048). The presence of pulmonary hypertension, right ventricular dilatation and tricuspid regurgitation correlated with the right heart failure after closure, and the atrial dimension, tricuspid regurgitation, and high filling pressure with new atrial arrhythmia. Fourteen patients died during follow-up. On multivariate analysis the main predictor of death was right heart failure (HR: 10; 95% CI 2,15-41). Conclusions: In terms of right heart remodeling, elderly patients still benefit from late ASD catheter closure. However, those who develop right heart failure after closure are at a high risk of death (HR:10). Diastolic dysfunction after the defect closure was not a predictor of death.
Abstract 15610: Long Term Health Related Quality of Life Outcomes Across the Therapeutic Spectrum in Patients With Congenitally Corrected Transposition of Great Arteries
Authors: Miza Salim Hammoud, Sohini Gupta, Olivia McCloskey, Lin Chen, Dominique L Tucker, Chang Yoon Doh, Paola Barrios, Rukmini Komarlu, Hani K Najm, Tara Karamlou
Journal: Circulation (2022)

Introduction: Congenitally corrected transposition of the great arteries (ccTGA) encompasses a diverse morphologic cohort with multiple treatment pathways. We characterized long term health related quality of life (HR-QoL) outcomes in adult patients with ccTGA across the therapeutic spectrum. Hypothesis: Methods: Between 1995-2020, 240 ccTGA patients were treated at the Cleveland Clinic. Of these, 59 adults were prospectively assessed with a hybrid PROMIS-10 and MacNew HR-QoL questionnaire at median follow-up of 10 years. Mental and physical scores were captured utilizing PROMIS 10 questionnaire, and social score from MacNew instrument. One-sample non-parametric sign tests evaluated deviations from referenced normative values. Differences among anatomic (AR) and physiologic repairs (PR) were assessed with Wilcoxon rank-sum test. Confidence intervals (95%) around measured means were generated from 1000 bootstrap samples. Results: Thirty one (18%) patients were female with median presentation age 26.3 years. Sixteen (27%) patients had PR, 12 (20%) had AR, 12 (20%) were medically managed, 5 (8.5%) had heart transplant and 3 (5.1%) underwent Fontan. Social scores were higher than the population norms (median= 6, P =.0002) for the overall cohort, but physical scores were lower than normative values (median = 44, P =.0183).Mental functioning was equivalent to normative values (median = 50, P =.9). AR and PR scores across domains were similar (Table 1). Conclusions: Adult patients living with ccTGA across the treatment spectrum have lower physical functioning than population norms. Despite these perceived physical impediments, social and mental functioning are unaffected. PR and AR had equivalent HR-QoL, providing important data to inform patient selection and triage.
Abstract 15388: A Randomized Placebo-Controlled Trial of Omega-3 Fatty Acids, Lycopene and Low Sodium Diet
Authors: Debra K Moser, Misook L Chung, Martha J Biddle, Mary Kay Rayens, Terry Lennie
Journal: Circulation (2022)

Background: Patients with heart failure (HF) commonly remain symptomatic after medical treatment. Symptoms are associated with rehospitalizations and mortality. We developed a 6-month nutrition intervention targeting the 3 most common HF symptoms: edema, shortness of air, and fatigue. The intervention involves 3 nutrients that target the pathologic pathways underlying symptoms: sodium, omega-3 fatty acids, and lycopene. Hypothesis: Time to first event will be longer in the nutrition intervention group than in the placebo group at 1-year follow-up. Methods: This was a randomized controlled double-blind clinical trial where 118 patients (mean age 63±12 years; 40% female; 64% NYHA class III or IV) with HF were randomized to active intervention vs placebo groups. The active intervention included a skill-building strategy based on Theory of Planned Behavior using Motivational Interviewing. It included a low sodium (LS) diet (2500mg sodium/day), lycopene supplementation daily (8 ounces [oz] of LS sodium tomato juice or 11.5 oz of LS V8 juice), and omega-3 fatty acid capsules (350mg EPA, 50 mg DHA/capsule) 3/meal with each meal. Placebo patients received generic instructions to follow a LS diet, 8 oz/day of fruit juice with no lycopene (e.g. cranberry juice) and capsules that contained soybean oil, but that looked like intervention capsules. Cox proportional hazards modeling was done to determine time to event of cardiac hospitalization or death based on intervention group. Models were adjusted for age, gender, NYHA class and HF medications. Results: The two groups were similar at baseline. The active intervention group had better event-free survival (Figure, p = 0.03) independent of covariates. Placebo patients were 2.2 (95% CI 1.025 - 4.584) times more likely to experience an event. Conclusion: A diet-based intervention aimed at the pathologic pathways underlying the 3 most common HF symptoms is successful in reducing cardiac rehospitalizations and mortality.
Abstract 15887: Bodyweight Changes and the Incidence of Atrial Fibrillation in Individuals With Obstructive Sleep Apnea
Authors: Jeffery Turley, Nicolette Friedman, N. Maritza Dowling, Ian Barrows, Zachary Falk, Dorys Melendez, Vivek Jain, Marco Mercader
Journal: Circulation (2022)

Introduction: Previous studies have demonstrated that obstructive sleep apnea (OSA) and obesity independently increase the risk for development of atrial fibrillation (AF). However, it is unknown whether weight changes in an OSA cohort also increase the risk of AF. Methods: This was a case control study from a single tertiary institution analyzing patients with a confirmed OSA diagnosis from 2013-2020. Patients with missing data on any of the key variables were excluded from these analyses. The covariates included smoking history, hypertension, congestive heart failure, chronic obstructive pulmonary disease, heart failure, and coronary artery disease. Patients’ weight at the time of AF diagnosis by electrocardiogram (ECG) was compared to the weight documented one year earlier. Weight at the time of the ECG closest to the sleep study date was compared to the weight one year prior for the control group. ​​Multivariate logistic regression analysis to examine the association between AF cases (versus controls) and weight percent change greater than 5%. Results: Among the 182 patients included in the analysis, the incidence of AF was 32.4% and the median weight change was -1.32± 11.69 lb (Table 1). About 36% of those diagnosed with AF had weight changes (gain or loss) above 5% compared to 23% in the control group (p = 0.07). The average weight change for those with diagnosed AF compared to individuals without AF was -2.5 ±11.8 lb vs. -0.76 ± 11.6 lb (p=0.19). The change in the adjusted odds of AF diagnosis among those with more than 5% weight gain or loss was 2.27 (95% CI =1.01, 5.09) compared to those with less or no weight change. Conclusions: Among individuals with OSA, those who exhibited weight changes greater than 5% over a one year period have increased odds for developing AF. Further large-scale studies need to be undertaken to understand the link between intentional versus unintentional weight loss.
Abstract 15377: Investigating the Role of Breast Cancer Susceptibility Gene 2 in High Glucose-Induced Endothelial Dysfunction
Authors: Sepideh Nikfarjam, Shuhan Bu, Hien Chi Nguyen, Berk Rasheed, Jefferson C Frisbee, Krishna Singh
Journal: Circulation (2022)

Introduction and Hypothesis: Mutations in the breast cancer susceptibility gene 2 (BRCA2) impair DNA damage repair which can eventually culminate in cancer, inflammation and/or apoptosis. Hyperglycemia-induced oxidative stress triggers DNA damage, inflammation and apoptosis, which are common contributors to endothelial dysfunction in diabetes. Here, we assessed the hypothesis that BRCA2 plays critical role in hyperglycemia-induced endothelial dysfunction. Methods and Results: Human umbilical vein endothelial cells (HUVECs) were exposed to high- (HG; 25 mM) or normal glucose (NG; 5 mM) and BRCA2 expression was measured. Our data showed significant BRCA2 upregulation in HG-treated HUVECs. Next, we successfully silenced BRCA2 in HUVECs, and measured the expression levels of p53 and p21 in HG- and NG-treated BRCA2-silenced HUVECs. We observed a significant upregulation of p53 and p21 in BRCA2-deficient HUVECs, which was further augmented by HG. Next, we measured the migratory and angiogenic potential of control and BRCA2-seilenced HUVECs under NG and HG. Our preliminary data showed that HG and loss of BRCA2 together inhibited the migratory capacity and angiogenic potential of HUVECs. To understand the mechanism behind the effect of HG on BRCA2-deficient ECs, we measured expression levels of endothelial nitric oxide synthase (eNOS). Both expression and activation of eNOS was reduced in HG-treated BRCA2-deficient HUVECs. To understand the effect of loss of BRCA2 on overall endothelial transcriptome and to understand mechanisms, we performed RNA sequencing on scrambled control- and siBRCA2-transfected HUVECs. Interestingly, a total of 3150 genes were differentially expressed in BRCA2-deficient HUVECs compared to the control group. Conclusion: Collectively, these findings reveal a novel role for BRCA2 as a regulator of endothelial function in context of HG treatment in vitro . Our RNA sequencing data shows theimportance of BRCA2 in regulating endothelial transcriptome and overall endothelial function. Further studies are underway; however, these results may provide important implications concerning the susceptibility of BRCA2 mutation carriers to HG-induced endothelial dysfunction as well as other CVDs.
Abstract 15307: Change in Cardiovascular Health, Cardiovascular Disease, and Mortality in Patients With Diabetes
Authors: Nzechukwu Isiozor, Donald Lloyd-Jones, Eugenie Valentin, Joshua J Joseph, Camille Lassale, Xavier Jouven, Bamba Gaye
Journal: Circulation (2022)

Aim: To describe patterns of change in cardiovascular health (CVH) measured by the Life’s Simple 7 (LS7) over 6 years in participants with diabetes, and assess the association of these patterns of change with subsequent CVD and all-cause mortality. Methods: We conducted a long-term prospective cohort analysis (median follow-up 19 years) using the ARIC study, a community-based, biracial cohort with participants aged 45-64 years at baseline in 1987-1989. Seven markers of LS7 were collected at baseline and 6 years later: smoking, body mass index, physical activity, diet, total cholesterol, blood glucose, and blood pressure. At both time points, participants were classified as low, moderate, and favorable CVH, corresponding to presenting 0-2, 3-4, and 5-7 metrics at ideal levels. Results: The majority (62.2%) of participants with diabetes at baseline had a stable low CVH at both visits, whereas 12.1% had stable moderate and 0.4% stable favorable, 14.9% improved, and 10.5% worsened. Compared to those with stable low LS7, CVD and mortality risk was lower for those who showed improvement 6 years later, or started moderate and remained so, or even who deteriorated to low CVH. This was driven by favorable changes in blood pressure, cholesterol, physical activity and smoking. Compared to participants free of diabetes with a stable favorable CVH trajectory, participants with diabetes had a higher CVD and mortality risk regardless of their CVH trajectory. However, those with a favorable LS7 trajectory displayed the same excess risk as participants without diabetes with constantly low CVH. Conclusions: Among individuals with diabetes, maintaining or reaching ideal levels of LS7 metrics can help reduce the excess CVD incidence and mortality. A favorable CVH trajectory in people with diabetes carried approximately the same excess CVD and mortality risk than an unfavorable CVH trajectory in people free of diabetes.
Abstract 15672: Cost-Effectiveness of Team-Based Care for Hypertension
Authors: Aditi S Rao, Kelsey B Bryant, Laura P Cohen, Nadine Dandan, Ian M Kronish, Nikita Barai, Valy Fontil, Yiyi Zhang, Andrew E Moran, Brandon K Bellows Pharmd
Journal: Circulation (2022)

Introduction: Team-based care (TBC), typically involving a physician and non-physician working in collaboration, is more effective than usual physician-only care in reducing blood pressure (BP). This analysis estimated the cost-effectiveness of TBC strategies vs. usual care over 10 years. Methods: We used the Cardiovascular Disease (CVD) Policy Model to project long-term BP, CVD events, and survival in a nationally representative cohort of 10,000 US adults (aged ≥20 years) with uncontrolled BP (≥140/90 mmHg) from the National Health and Nutrition Examination Survey. We compared (1) usual care, (2) TBC with a registered nurse providing hypertension counseling, and (3) TBC with a pharmacist providing counseling and titrating medications. BP reductions with TBC were derived from meta-analysis; other inputs were derived from published literature and publicly available data. TBC interventions were simulated to last six months, after which individuals were assumed to return to usual care. The outcomes were mean per-patient direct healthcare costs (2021 USD), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) from a US healthcare sector perspective. Sensitivity analyses assessed the impact of TBC program design and hypertension care process parameters on the cost-effectiveness of TBC. Results: The mean (SD) age was 59.8 (16.6) years, 50.0% were female, and mean baseline systolic BP was 150.9 (14.2) mmHg. At 10 years, TBC with nurse counseling and with pharmacist titration were projected to result in mean (95% uncertainty interval) 0.6-mmHg (0.4, 0.8) and 2.8-mmHg (2.2, 3.4) greater reductions in systolic BP. Both TBC strategies were estimated to dominate (i.e., cost less and more effective) usual care, with nurse counseling projected to cost -$617 (-$1539, $364) and with pharmacist titration -$416 (-$1400, $470) less than usual care. Compared with TBC with nurse counseling, TBC with pharmacist titration had an ICER of $13,000/QALY gained (88.0% probability ICER &lt;$50,000/QALY gained). The ICER was most sensitive to the probability of pharmacist medication intensification. Conclusions: TBC with pharmacist titration is a cost-effective strategy to reduce CVD events in US adults with uncontrolled hypertension.
Abstract 15560: Mitophagy Dysfunction and Activation of the Inflammasome Cause Aortic Stiffness in Low Aerobic Capacity Aged Rats
Authors: Chandrika Canugovi, Mark Stevenson, Aleksandr E Vendrov, Andrey Lozhkin, Lauren G Koch, Steven Britton, Marschall Runge, Nageswara R Madamanchi
Journal: Circulation (2022)

Aging and low aerobic capacity are associated with an increased risk of cardiovascular events and mortality. We reported that a polygenic rat model selectively bred for low aerobic capacity (LCR) showed aortic stiffness and dysfunction with age compared to rats bred for a high aerobic capacity (HCR). We observed increased aortic mitochondrial ROS and extracellular mtDNA DAMPs levels, activation of AIM2 inflammasome and its downstream effectors and increased collagen content in old LCR rat aortas. However, the molecular mechanisms linking low aerobic capacity to inflammation in aging have not been elucidated. In order to decipher the changes in genetic networks in low aerobic capacity and aging-associated aortic stiffness, a global transcriptome analysis was performed by RNA-Seq and gene ontology analysis of aortas from young (4 month) and old (27 month) LCR and HCR rats. Down-regulated pathways in old LCR aortas include mitochondrial biogenesis and mitophagy and up-regulated pathways include pro-inflammatory pathways, apoptosis/necroptosis/ferroptosis pathways, in contrast to HCR aortas which have higher levels of pathways regulating longevity, oxidative phosphorylation, and mitophagy and autophagy. In line with that, old LCR rats displayed a 54% reduction in mitophagy (colocalization of mitochondrial marker protein TOM20 with lysosomal marker protein LAMP1) in aortic media and a 76% reduction in cultured VSMCs in comparison to older HCR rats. Mitophagy levels did not differ significantly between young LCR and HCR rats. The autophagic vacuole formation rate was a 12-fold lower in old LCR than in old HCR aortic VSMCs, suggesting that impaired mitophagy may be responsible for accumulation of mtDNA-derived damage associated molecular patterns (mtDNA DAMPs). Treatment with various inducers of mitophagy (rapamycin, deferiprone, and MitoTEMPO) significantly increased mitophagy and decreased mtDNA DAMPs levels in old LCR VSMCs. This was also associated with a reduction in inflammasome activation, mitochondrial dysfunction, and ROS levels. We conclude that impaired mitophagy causes accumulation of DAMPs and inflammasome activation, inducing aortic stiffness and dysfunction in old age LCR rats.